Endocrine Abstracts

JOINT2644

Background: Osteogenesis imperfecta type V (OI-V), driven by the recurrent IFITM5 c. -14C>T mutation, is characterized by fractures, hyperplastic callus formation, and progressive interosseous membrane calcification. Despite bisphosphonate use in OI management, their long-term efficacy in OI-V remains poorly defined. This study evaluates phenotypic variability and longitudinal bisphosphonate outcomes in the largest OI-V cohort to date.

Methods: This 8-year retrospective analysis included 143 molecularly confirmed OI-V patients from 105 unrelated families (median age: 12. 4 years; follow-up: 8. 4 years). Patients received intravenous bisphosphonates (zoledronic acid: 0. 05 mg/kg/6 months; pamidronate: 1 mg/kg/day ×3 days/4 months). Clinical, radiographic (spinal radiographs, DXA), and biochemical markers (β-CTX, P1NP, calcium, phosphate, 25-OH-vitamin D) were analyzed.

Results: All patients carried the IFITM5 c. -14C>T variant. Phenotypic features included radial head dislocation (57. 8%; median onset: 10. 2 years), interosseous membrane calcification (85%; earliest onset: 4 years), and hyperplastic callus (52. 3%; onset: 4–8 weeks post-fracture). Bisphosphonate therapy (median initiation age: 5. 2 years) reduced annual fracture rates from 2. 1 to 0. 4, improved lumbar spine BMD Z-scores (−2. 6 to −1. 3), restored vertebral height in 68% (>15% increase), and elevated height Z-scores (−2. 5 to −1. 8). Bone turnover markers declined (β-CTX: ↓42%, P1NP: ↓38%). However, JOINT deformities and ectopic calcification progressed despite treatment: radial head dislocation prevalence increased from 24% (<10 years) to 82% (>15 years), correlating with reduced elbow mobility (r = −0. 71, P<0. 001).

Conclusions: Bisphosphonates significantly improve bone density and reduce fractures in OI-V but fail to halt ectopic calcification or JOINT degeneration. These findings underscore the need for early rehabilitation and novel therapies targeting pathological ossification. This study refines the clinical spectrum of OI-V and provides critical evidence for optimizing multidisciplinary management strategies.